The following includes-information that may be useful in understanding the present inventions. It is not an admission that any of the information provided herein is prior art, or relevant, to the presently described or claimed inventions, or that any publication or document that is specifically or implicitly referenced is prior art.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. It affects the neurons in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. When the motor neuron dies, the ability of the brain to initiate and control muscle movement is lost. The name Amyotrophic lateral sclerosis means when the muscle (“Myo”) does not (“A”) receive nourishment (“Trophic”), the muscles “atrophies” or wastes away. This leads to the local area (“lateral”) of muscles where portion of the nerve cells signal and control the muscles degenerates and leads to scarring or hardening (“sclerosis”) in the local area. As ALS disease progresses, people lose the ability to speak, cat, move and breathe. The motor neurons that provide voluntary movements and muscle control dies. In the ALS patient's own words, they are watching themselves dying off a little each day, trapped in a body that cannot move.
Amyotrophic Lateral Sclerosis (ALS, also known since the late 1930s as Lou Gehrig's Disease, and also known as motor neuron disease in other countries) is a uniformly-fatal neurodegenerative disease in which the neurons controlling the voluntary skeletal muscles wither and die. This renders the patient progressively paralyzed until respiratory failure finally ends life. The average survival from diagnosis is between 2-5 years. The disease was first described in medical literature by Jean-Martin Charcot in 1869 and 145 years later there is still no truly-effective treatment for this savage disease (Xiong Z Q et al. 2002, Fas(t) balls and Lou Gehrig disease. A clue to selective vulnerability of motor neurons? Neuron. 12: 35 (6): 1011-1013).
ALS was for approximately 100 years thought to be a cell-autonomous disease in which some intrinsic failing of the motor neurons alone caused their death. Since the turn of last century, after discovery of the first genetic cause and subsequent development of the transgenic rodent model, the disease has been realized to be non-cell-autonomous. In fact, it is now understood that multiple cellular and support systems are involved in the development and progression of ALS. (Ilieva H, et al. 2009. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and Beyond. J Cell Biol. 187:761-772.). Addressing only a single pathway is therefore unlikely to produce enough benefit to successfully treat a multi-factor disease.
Most drug actions are single targeted by either increasing the desired target (agonist) or decreasing the undesirable target (antagonist). For example, if the over expression of X causes certain disease, the drug can be an antibody binding to X to decrease its presence.
Central Nervous system diseases are very complex and involve more than a single disease pathway or a single target. What is needed is a high level upstream master regulator which is active and functional in the nervous system development at the embryonic stage, one that may provide multi-targeted therapeutic effect. The invention satisfies this need. An MNTF analog GM604 was shown to have therapeutic effect through modulating multi-targets is an aspect of the invention. GM604 is the name assigned for ALS therapeutic treatment. GM602 is assigned for ischemic stroke treatment. GM608 is assigned for Parkinsonigned for treatment.